AGA recommends all patients with colorectal cancer get tested for Lynch syndrome

All colorectal cancer patients should undergo tumor testing to see if they carry Lynch syndrome, the most common inherited cause of colorectal cancer, according to a new guideline¹ published in Gastroenterology, the official journal of the American Gastroenterological Association.

"Approximately 50,000 Americans are expected to die from colorectal cancer this year, and hereditary syndromes account for a small, but important fraction of those diagnoses," said Joel H. Rubenstein, MD, AGAF, lead author of the guideline, research scientist at the Veterans Affairs Center for Clinical Management Research and associate professor, division of gastroenterology at the University of Michigan Medical School. "The majority of patients with Lynch syndrome are unaware that they have the syndrome. The AGA recommendation for tumor testing in all newly diagnosed cases of colorectal cancer to identify Lynch syndrome could be considered as a process measure to ensure that patients are receiving the highest quality of care."

AGA developed the guideline using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and best practices as outlined by the Institute of Medicine. The recommendations on the diagnosis and management of Lynch syndrome follow; review the full guidelines for information on the strength of the recommendations.

• Patients with a family history suggestive of Lynch syndrome, but no personal history of cancer: Offer patients the option of risk prediction modelling for testing, rather than doing nothing.
• Patients with a family history suggestive of Lynch syndrome, but no personal history of cancer: Offer patients the option of risk prediction modelling for testing, rather than proceeding directly to germline testing.
• Patients with colorectal cancer: Test tumor either with immunohistochemistry (IHC) or for microsatellite instability (MSI). Lynch syndrome tumors display high MSI.
• Patients with colorectal cancer with IHC absent for MLH1, approximately 75 percent of whom will have sporadic cancers rather than Lynch syndrome: Test tumor for BRAF mutation or hypermethylation of the MLH1promoter; if patient has neither, conduct germline testing for Lynch syndrome.
• Patients with Lynch syndrome: Surveillance colonoscopy, rather than doing nothing.
• Patients with Lynch syndrome: Perform surveillance colonoscopy every one to two years versus less frequent intervals.
• Patients with Lynch syndrome: Offer aspirin as cancer chemoprevention.

Colorectal cancer is the second leading cause of cancer death in the U.S. Approximately 30 percent of persons diagnosed with CRC have a family history of the disease, and 5 to 6 percent have mutations that are diagnostic of a known hereditary cancer syndrome. Lynch syndrome is the most common inherited cause of colorectal cancer. Approximately 700,000 Americans have Lynch syndrome, and children have about a 50 percent chance of inheriting the disorder. However, the majority of people with Lynch syndrome don't know that they have it. People with Lynch syndrome have a mutation of the MMR gene, which means that their bodies are less able to fix errors in the DNA. While not all people with Lynch syndrome will develop cancer, a person who has the mutation is more likely to get certain types of cancer, including an 80 percent higher risk of colorectal cancer and a 60 percent higher risk of endometrial cancer.

Read the technical review.² AGA also offers a Clinical Decision Support Tool and a patient guide³ for the Lynch syndrome guideline.